Cyclosporin A a is new imunmo-suppressive agent used in organ transplantation to prevent rejection, counteract graft-versus-host disease, and facilitate specific transplantation tolerance. On a cellular level it prevents the development of cytotoxic effector cells and facilitates the development of suppressor effector cells. Clinically its major toxicity is renal failure, which is so far unpredictable and can be duplicated in a rat model. Predicitive parameters need to be identified, using pharmaco-toxicologic approaches, and measures need to be evaluated that can prevent or counteract the clinically experienced side effects of CsA. A better understanding of the mechanism of action of CsA on a cellular and subcellular level will aide in this goal, as will the description of the action of CsA on lymphocyte responses to antigens other than transplatation antigens. Apart from aiding the clinician, giving him a better rationale for using CsA and improving the therapeutic ratio of CsA, these studies will help to identify the mechanism of tolerance towards self and non-self by using CsA as an immunobiological tool in syngeneic and allogeneic bone marrow and skin transplantation models.